pUDK-HGF Gene Therapy to Relieve CLI Rest Pain and Ulcer: A Phase II, Double-Blind, Randomized Placebo-Controlled Trial

• Published in: Human gene therapy Vol. 32; no. 15-16; p. 839
• Main Authors: Gu, Yongquan, Cui, Shijun, Liu, Changjian, Zhao, Jichun, Li, Ming, Li, Yiqing, Yang, Xinglong, Lv, Bonan, Li, Mingzhang, Zhao, Wenguang, Guo, Wei, Huang, Jianhua, Huang, Wen, Qiu, Zhenming, Zhao, Jun, Yin, Ping, Qin, Tingting, Zhu, Dan, Sun, Wenjie, Ren, Keyun, Lu, Yuxin, Cheng, Xiaochen, Du, Li, Xiao, Fengjun, Zhang, Qinglin, Wu, Zuze
• Format: Journal Article
• Language: English
• Published: United States 01-08-2021
• Subjects: Chronic Limb-Threatening Ischemia; Genetic Therapy; Hepatocyte Growth Factor - genetics; Humans; Ischemia - therapy; Pain; Ulcer; gene therapy; peripheral arterial disease; critical limb ischemia; pUDK-HGF; hepatocyte growth factor; phase II clinical trial
• ISSN: 1557-7422
• DOI: 10.1089/hum.2020.290

This phase II clinical trial investigated the efficacy and safety of intramuscular injection of plasmid pUDK-HGF, which encodes the human hepatocyte growth factor gene in patients with critical limb ischemia. Resting pain patients (
 = 119) and patients with leg ulcers (
 = 121) were enrolled as two cohorts and randomized to receive pUDK-HGF treatment on days 0, 14, and 28. In the resting pain cohort, the proportion of patients with complete pain relief on day 180 after receiving pUDK-HGF injection, as the primary outcome, was significantly higher than that of the placebo group on the same day (
 = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups (
 = 0.0168). In the ulcer cohort of patients, pUDK-HGF treatment tended to be superior to the placebo in the percentage of patients with both complete ulcer healing and >50% ulcer healing. No significant differences in the incidence of adverse events (AEs) or serious AEs were observed among the groups. The mid-dose pUDK-HGF (6 mg) was the most efficacious, and is therefore an appropriate dose for use in a phase III clinical trial. This study was approved by the China Food and Drug Administration (2013L00637), China Clinical Trial Registry URL: www.chinadrugtrials.org.cn. Unique Identifier: 20130378.